Diabetes is a devastating disease that is caused by either the complete destruction of the pancreatic beta-cell (type I, or juvenile diabetes) or the deterioration of the function of such cells (Type II, or adult diabetes). Many people suffer from the diseases, with an estimated number in this country of app. 17.5 million diagnosed. As a percentage of the total population, this figure is rising. Associated health costs as outlined by the American Diabetes Association are estimated at $174 billion, of which one third is accredited to a loss of national productivity. The average cost for health care expenses for a diabetic person is 2.3 fold higher than in absence of diabetes, and is currently set at $11,744/year.
Temporal curing of diabetes has been achieved. Presently, a sparse supply of organ donor cadaveric human islets can be used to transplant a limited number of type I diabetic patients. Such recipients become insulin-independent, for periods now up to several years.
The etiology of the disease is related to the role of the pancreatic insulin-producing cell, the beta cell. The normal function of the pancreatic beta cell is to control blood glucose homeostasis, and in absence of such regulation several detrimental effects are observed in patients with the disease, even in the presence of intensive treatment. Such long-term complications affect the function of the kidneys (nephropathy), eye degeneration (retinopathy), loss of extremities by amputation (vascular complications) and diabetes is furthermore associated with increased cardiovascular risk, and results in a shortened lifespan.
In both type I and type II diabetes, focus is on the life and function of the pancreatic beta cell. This cell type is unique in multiple aspects, the most important being that it is the only cell type in the body capable of producing insulin. Consequently, a loss of such cells leads to insulin dependence. Type I or type II diabetes is diagnosed at a point where the function of such cells have decreased to a level not meeting initial demand for appropriate blood glucose lowering following a meal. It is generally believed, however, that if one could assess beta cell mass, and function prior to diagnosis, intervention strategies may be applied to circumvent the further demise of the failing cell population. For type I diabetes, current focus is on identifying the presence of circulating anti-islet auto-antigens, as such may help identify those children that are at-risk, or are overtly pre-diabetic due to an ongoing immune destruction. For type II diabetes, current focus is on establishing clinical testing, such as the use of oral glucose tolerance testing (OGTT), now suggested as a standard evaluation of males approaching 50 years of age. The result of an OGTT can help identify individuals that are at the pre-diabetic point, and interventions can be performed, mostly including counseling related to the benefits of lifestyle changes involving increased exercise, caloric intake, and balancing diets. In both cases, non-invasive imaging of the beta cell mass, if aided by reagents capable of marking the cell population, could substantially improve the diagnostic toolbox.
Presently, there is no method by which beta cell mass can be assessed in a non-biased manner non-invasively in human subjects. Accurate measurement of beta cell mass in pancreas is dependent on biopsy analysis followed by histological assessment of beta cell numbers and morphometric counting; in most cases obtained post-mortem through autopsy material. The amount of donor material reflecting on progressive disease development is therefore significantly limited, and kinetic studies on disease progression in an individual are impossible using this technology. Another important aspect related to a growing need for beta cell mass assessment is following islet transplantation. Although only performed in few individuals, this technology is becoming more widespread. It is carried out by isolating an islet-enriched cellular fraction from a human donor post-mortem, which is subsequently transplanted through portal vein injection into a HLA-matched type I diabetic recipient. Following transplantation, there is generally no means to assess the viability and health of the grafted islet cells, as these are inaccessible in the recipient's liver vascular system. A general assessment of graft function is determined by measurements of insulin-dependency, gradually lowering injected insulin as cells in the graft become capable of providing insulin. Often, multiple transplants are required, empirically defined based on outcome. There is no unbiased assessment of the actual viable islet cell mass that engrafts within the liver, and it cannot be followed. It should be mentioned that given the local production of insulin by such grafted islets, a local adipogenic effect occurs within the liver, and such changes may be measured non-invasively by MRI. However, in the best case, this only provides a read out of grafting efficiency; it is not able to accurately measure numbers/mass of viable grafted islet cells.
Thus, a need exists for methods of assessing beta cell mass and/or activity non-invasively.